Future research should focus on the biomechanical factors associated with agility-related injuries.”
“We investigate size dependent strengthening mechanisms in sputtered Fe/W multilayers with individual layer thickness, h, varying from 1 to 200 nm. Microstructure analyses reveal that Fe/W has incoherent bcc/bcc interface when h is greater than 5 nm. When h decreases to 1-2.5 nm, the interface becomes semicoherent, and Fe and W show significant lattice distortions comparing to their bulk counterpart due to interface constraint. The layer thickness dependent drastic variations in x-ray diffraction profiles

are simulated well by using an analytical model. Film hardness SNX-5422 increases with decreasing h, and approaches a maximum value of 12.5 GPa when h is 1 nm. The layer thickness dependent film hardnesses are compared with

analytical models. Koehler’s image force plays a major role in determining the maximum strength of composites at smaller h. (C) 2010 American Institute of Physics. [doi:10.1063/1.3400130]“
“It is now widely accepted that a gross change in the maternal diet during pregnancy results in offspring with raised blood pressure. More recently, results from human intervention studies and a range of animal experiments have questioned this concept. It thus appears that, when blood pressure is measured selleck screening library directly or by telemetry, the extent to which blood pressure is raised is largely dependent on the magnitude of the postnatal catch-up growth. In addition, such effects can be lost when appropriate corrections are made

for current body weight. Consequently, offspring born to nutritionally manipulated mothers can actually have a lower blood pressure than control group offspring. At the same time, studies of the offspring born to contemporary women in developed countries show very little, if any, effect of changes in maternal diet on blood pressure in the offspring when assessed during childhood. In small animal studies, at BI 6727 least, the cardiovascular outcomes linked to small size at birth can differ between the sexes, which may be related in part to differences in kidney function between males and females. With respect to large animal studies, significant effects on blood pressure are less apparent and may relate to the much slower onset of hypertension. The challenge is to use our increased knowledge of the critical windows in early development to optimize later health. One clear priority is the prevention of excess adiposity and to determine how epigenetic mechanisms may provide novel strategies in this regard. Am J Clin Nutr 2009; 89(suppl): 1518S-22S.”
“Landfill leachates are generated from municipal solid waste landfills under the action of water percolating through the landfilled waste.

We aimed to determine 1) which patient and vein characteristics affected the AVVQ score, and 2) whether scores differed between those who were and were not offered treatment.

Methods: Patients completed the AVVQ at the clinic prior to being seen. Treatment was offered to patients AZD7762 with symptoms, and duplex detected truncal incompetence by surgeons blinded to the score.

Results: A total of

228 consecutive patients completed the AVVQ: 199 were valid questionnaires. On multivariate analysis, factors associated with a worse quality of life were female gender (p = .034, 3.14 mean unit increase in AVVQ), and bilateral varicose veins (10.25 unit increase, p < .001). For patients with C2 disease, only the presence of bilateral veins was significant.

Overall, the AVVQ score was higher in those patients offered treatment than in those who were not (mean 20.3 [SD = 9.9] vs. 17.3 [SD = 10.3], p = .023), which equates to a 2.74 unit increase. SB203580 This was not significant in patients with C2 disease.

Conclusion: It is unlikely that a threshold AVVQ score could be used to aid referral of patients with C2 disease. The distribution of veins (unilateral vs. bilateral) must be adjusted for when reporting AVVQ scores. (C) 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.”
“A new sesquiterpenoid, 1 alpha,4 beta,7 beta -eudesmanetriol (1), was isolated together Selleck PD-1/PD-L1 Inhibitor 3 with the known compounds 1 beta,4 beta,7 beta -eudesmanetriol (2) and oplopanone (3) from the rhizomes of Homalomena sagittifolia. The structures of these compounds were determined by extensive spectral analyses. The compounds 1 and 2 inhibited growth of Pseudomonas

stutzeri with a MIC value of 117 mu M when evaluated for antibacterial activity using the minimum concentration assay. Both these compounds showed remarkable activities against acetylcholinesterase enzyme with IC50 values ranging between 25 and 26 mu M. The isolation of these sesquiterpenoids and their biological activities observed in this study support the reported traditional uses of H. sagittifolia for the treatment of microbial related diseases and central nervous system disorders.”
“The cerebral state index (CSI) is used for monitoring EEG and depth of anaesthesia. The objective of this study was to analyse the correlation between ocular reflexes, CSI and estimated propofol plasma concentrations (PropCP) in dogs during induction of anaesthesia with propofol.

Fourteen dogs were premedicated with acepromazine 0.05 mg kg(-1) IM. Anaesthesia was induced with a 200 ml h(-1) propofol 1% constant infusion rate until loss of corneal reflex using RugLoop 11 software with Beths’ pharmacokinetic model to estimate PropCp.

However, the surgical invasiveness of HPD is considerable.

We present our treatment option for patients with distal bile duct cancer showing mucosal spreading to the hepatic hilum associated with impaired liver function. To minimize resection volume of the liver, an isolated caudate lobectomy (CL) with pancreatoduodenectomy (PD) using an anterior liver splitting approach is

presented. Liver transection lines and bile duct resection points correspond complete with our standard right and left hemihepatectomies with CL for perihilar cholangiocarcinoma.

Total operation selleck compound time was 765 min, and pedicle occlusion time was 124 min, respectively. Although the proximal mucosal cancer extension was identified at both the right and the left hepatic ducts, all resection margins were negative for cancer.

Isolated AZD6094 mw CL with PD is an alternative radical treatment option for bile duct cancer patients with impaired liver function.”
“Objective. We performed a systematic review of the literature to evaluate the effects of alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes mellitus. Research design and methods. The databases MEDLINE and EMBASE were searched using the key words “”lipoic acid”", “”thioctic

acid”", “”diabet*”", and the MeSH-terms “” thioctic acid”" and “” diabetes mellitus”". Randomised controlled trials using the TSS score as the outcome measure were selected and assessed for their methodological quality. Study selection and quality assessment were performed independently by three observers. Results. Overall, the pooled standardized mean difference

estimated from all trials revealed a reduction in TSS scores of -2.26 (CI: -3.12 to -1.41; P = 0.00001) in favour of alpha lipoic acid administration. Subgroup analyses of oral administration (-1.78 CI: -2.45 to -1.10; P = 0.00001) and intravenous administration RG-7388 (-2.81 CI: -4.16 to -1.46; P = 0.0001) confirmed the robustness of the overall result. Conclusions. When given intravenously at a dosage of 600 mg/day over a period of 3 weeks, alpha lipoic acid leads to a significant and clinically relevant reduction in neuropathic pain (grade of recommendation A). It is unclear if the significant improvements seen after 3-5 weeks of oral administration at a dosage of >= 600 mg/day are clinically relevant.”
“Laboratory monitoring of amiodarone therapy is recommended due to the high incidence of adverse events associated with the drug. The use of appropriate monitoring is unknown at pediatric hospitals. The Pediatric Health Information System database was queried during a 5-year period for all patients who received amiodarone while hospitalized. Use of thyroid function testing, hepatic function testing, electrocardiogram, pulmonary function testing, and chest X-ray for patients was identified.

Results: BKM120 PI3K/Akt/mTOR inhibitor The release of zoledronic acid was greatest during the first twenty-four hours for all concentrations and decreased rapidly during the next forty-eight hours to reach a plateau after four days. The proliferation assay

(MTT) showed zoledronic acid to have significant cytotoxicity in cultures of stromal giant cell tumor, multiple myeloma, and renal cell carcinoma cells. In addition, zoledronic acid decreased the number of viable tumor cells in a dose-dependent manner. Renal cell carcinoma from bone (RBM1-IT4) and stromal giant cell tumor of bone were more susceptible to zoledronic acid than was multiple myeloma.

Conclusions: The method presented in our study is a reproducible technique for evaluating zoledronic acid elution from bone cement and determining its impact on tumor growth. Zoledronic acid is released from bone cement, remains biologically active despite the polymerization of cement, and inhibits the in vitro growth of cell lines from giant cell tumor of bone, myeloma, and renal cell carcinoma.”
“Objective: There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. In

chondrocytes, accumulation of O-GlcNAcmodified proteins induces hypertrophic Autophagy inhibitor differentiation. Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. However, the mechanisms responsible for these changes have not been described. Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage

of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC).

Design: Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. HOC were cultured and stimulated with the catabolic cytokine IL-1 alpha. Global protein O-GlcNAcylation and the synthesis of the key NU7441 DNA Damage inhibitor enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot.

Results: OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. In HOC, IL-1 alpha stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis.

onclusions: Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification.

Grain boundaries with low interface energy are concluded to be preferable to weaken recombination activity by the gettering process and improvement of solar cell performance based on mc-Si. c 2011 American Institute of Physics. [doi:10.1063/1.3544208]“
“Objective. The aim of the study was to investigate treatment outcome of mandibular advancement devices (MADs) for positional and nonpositional obstructive sleep apnea (OSA).

Study design.

Forty-two positional (supine apnea-hypopnea index [AHI] find more >= 2 times lateral AHI) and 30 nonpositional (supine AHI < 2 times lateral AHI) OSA patients performed 2-nights of sleep study before and after insertion of MADs.

Results. The decreases in apnea severity based on a reduction in the overall and supine AHI values after MADs therapy were significantly

greater for the positional OSA than nonpositional OSA group. A multiple linear regression analysis showed that decrease in overall AHI was significantly associated with being in the positional group (standardized coefficient = 0.505). Age, body mass index, gender, and time in supine position during sleep did not show significant associations with decrease in overall AHI after MAD therapy.

Conclusion. Our data suggest that MADs are more effective in positional OSA than nonpositional OSA patients. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 724-731)”
“Plasma-induced damage to porous SiOCH (p-SiOCH) films during organic resist film ashing using

dual-frequency capacitively coupled O(2) plasmas was investigated MK2206 using the pallet for plasma evaluation method developed by our group. The damage was characterized by ellipsometry and Fourier-transform infrared spectroscopy. Individual and synergetic damage associated with vacuum ultraviolet (VUV) and UV radiation, radicals, and ions in the O(2) plasma were clarified. It was found that the damage was caused not only by radicals but also by synergetic reactions of radicals with VUV and UV radiation emitted by the plasmas. It is noteworthy that the damage induced by plasma exposure without ion bombardment was larger than the damage with ion bombardment. Go 6983 clinical trial These results differed from those obtained using an H(2)/N(2) plasma for resist ashing. Finally, the mechanism of damage to p-SiOCH caused by O(2) and H(2)/N(2) plasma ashing of organic resist films is discussed. These results are very important in understanding the mechanism of plasma-induced damage to p-SiOCH films. (C) 2011 American Institute of Physics. [doi:10.1063/1.3544304]“
“Objective. This study compares synchronous oral squamous cell carcinomas (OSCCs) with single primary OSCCs to assess the histopathologic parameters with a known prognostic significance.

Study design. Twenty-eight cases of synchronous OSCCs and a control group of single primary OSCCs were compared for 15 histologic prognostic variables.

Results.

Using plastid transformation, we have integrated different versions of the Escherichia coli IS element IS150 into the plastid genome of tobacco (Nicotiana tabacum) plants. We show that IS150 is

faithfully mobilized inside the chloroplast, and that enormous quantities CBL0137 concentration of transposition intermediates accumulate. As synthesis of the IS150 transposase is dependent upon programmed ribosomal frame shifting, our data indicate that this process also occurs in chloroplasts. Interestingly, all insertion events detected affect a single site in the plastid genome, suggesting that the integration of IS150 is highly sequence dependent. In contrast, the initiation of the transposition process was found to be independent of the sequence context. Finally, our data also demonstrate that plastids lack the capacity to repair double-strand breaks in their genomes by non-homologous end joining, a finding that has important implications for genome

stability, and which may explain the peculiar immunity of the plastid to invading promiscuous DNA sequences of nuclear and mitochondrial origin.”
“Background: The optimal strategy for promoting self-care for heart failure (HF) is unclear.

Methods and Results: We conducted a randomized trial to determine whether a “”teach to goal”" (TTG) educational and behavioral Nepicastat inhibitor support program provided incremental benefits to a brief (1 hour) educational intervention (BEI) for knowledge,

self-care GS-7977 inhibitor behaviors, and HF-related quality of life (HFQOL). The TTG program taught use of adjusted-dose diuretics and then reinforced learning goals and behaviors with 5 to 8 telephone counseling sessions over 1 month. Participants’ (n = 605) mean age was 61 years; 37% had marginal or inadequate literacy; 69% had ejection fraction <0.45; and 31% had Class III or IV symptoms. The TTG group had greater improvements in general and salt knowledge (P < .001) and greater increases in self-care behaviors (from mean 4.8 to 7.6 for TTG vs. 5.2 to 6.7 for BEI; P < .001). HFQOL improved from 58.5 to 64.6 for the TTG group but did not change for the BEI group (64.7 to 63.9; P < .001 for the difference in change scores). Improvements were similar regardless of participants’ literacy level.

Conclusions: Telephone reinforcement of learning goals and self-care behaviors improved knowledge, health behaviors, and HF-related QOL compared to a single education session. (J Cardiac Fail 2011;17:789-796)”
“Methylmercury (MeHg), a known neurotoxin, has been reported to alter glutamate homeostasis in the neuronal environment resulting in excitotoxicity. This study was conducted to investigate whether, and if so, under what conditions, that low dose MeHg would enhance the toxicity of glutamate and to what extent that blockade of NMDA receptors would alter MeHg and glutamate’s toxicity in cultured neuroblastoma cells.

2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine SBE-β-CD molecular weight (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine.

To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag (R) conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O-2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine

(vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM).

Conclusions: The atmospheric generators for capnophilic bacteria Genbag CO2 (R) is an appropriate technology that can be transferred to the field for epidemiological surveys of drug-resistant malaria. The present data suggest the importance of the gas mixture on in vitro microtest results for anti-malarial drugs and the importance

of determining the microtest conditions before comparing and analysing the data from different laboratories and concluding on malaria resistance.”
“Between January 2000 and July 2009, 132 individuals inquired about altruistic kidney donation to strangers. These donors were willing to donate to genetically and emotionally unrelated patients. Some altruistic donors wished to donate to a specific person, but most wished to donate anonymously. In domino-paired Z-DEVD-FMK Apoptosis inhibitor donation, the altruistic donor donates to the recipient of an incompatible couple; the donor of that couple (domino-donor) donates to another couple or to the waiting list. In contrast to kidney-exchange donation where bilateral matching of couples is required, recipient and AZD6738 donor matching are unlinked in domino-paired donation. This facilitates matching for unsuccessful couples from the kidney-exchange program where blood type O prevails in recipients and is under-represented in donors. Fifty-one altruistic donors (39%) donated their

kidney and 35 domino-donors were involved. There were 29 domino procedures, 24 with 1 altruistic donor and 1 domino-donor, 5 with more domino-donors. Eighty-six transplantations were performed. Donor and recipient blood type distribution in the couples limited allocation to blood type non-O waiting list patients. The success rate of domino-paired donation is dependent on the composition of the pool of incompatible pairs, but it offers opportunities for difficult to match pairs that were unsuccessful in the kidney-exchange program.”
“Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively referred to as malignant gliomas.

“
“The role of human papillomavirus (HPV) in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa), whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67%) patients had positive S63845 expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall

survival (OS) (median 4.59 years) compared to HPV-negative (median 8.24 years, P = 0.0381). In multivariate analysis age (P < 0.001), Gleason score (P < 0.001), nuclear grading

(P = Cyclopamine clinical trial 0.002), and HPV status (P = 0.034) were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.”
“Background: The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits access to new medicines based on an assessment of cost relative to clinical benefit. Those drugs that are expensive and provide modest benefits will be less likely to receive a government price subsidy. There is concern that the cost-effectiveness hurdle will limit access to new cancer treatments because of their high costs and modest benefits.

Objective:

To test the hypothesis that Ceteris paribus, cancer drugs are less likely to receive a recommendation for reimbursement on the Pharmaceutical Benefits Scheme (PBS) than non-cancer drugs.

Methods: We reviewed public summary documents (PSDs) on all major submissions considered by the Citarinostat Pharmaceutical Benefits Advisory Committee (PBAC) from July 2005 to March 2008. Each PSD includes summary information on the clinical, economic and utilization considerations of the PBAC in arriving at a recommendation. A total of 227 PSDs were reviewed, from which 243 PBAC recommendations were identified. Logistic regression was used to determine the effects of drug type (cancer vs non-cancer) and other potentially confounding variables on the outcome of PBS approval versus non-approval.

Results: There were 243 PBAC recommendations in 227 published PSDs: 108 for rejection (44%), 10 deferrals (4%) and 125 (51%) recommendations for listing. Recommendations for listing were made somewhat more often for non-cancer drugs than for cancer drugs: 104/191 (54%) versus 21/52 (40%), respectively; p=0.07.

Then, a further knowledge about the kinetic mechanism click here of melanogenesis is required prior to its possible industrial utilization. In this work, an autocatalytic kinetic model to explain melanin formation from L-tyrosine using mushroom tyrosinase and measuring the absorbance of the solution has been

developed and fitted to experimental data. This expression allows to describe melanin formation as a function of time of reaction, including some important parameters such as the extinction coefficient. Absorbance will start growing after a lag period in which colorless intermediates are produced. The extinction coefficient of the resulting products is not a constant value, because it depends on the conditions of each experiment. Tyrosinase seemed to have a lower catalytic effect on L-tyrosine than on L-DOPA. (C) 2009 Elsevier Ltd. All rights reserved.”
“Toxoplasmosis is a global zoonosis caused by Toxoplasma gondii, an intracellular apicomplexan parasite. The objectives of this study were to estimate Entinostat the animal and flock level seroprevalence and risk factors associated with toxoplasmosis in goats of Central Ethiopia. In Ethiopia, goats are economically important animals used for meat and milk production. The study was cross-sectional

and 927 blood samples from 187 goat flocks were collected to examine T. gondii specific IgG antibodies by enzyme linked immunosorbent assay (ELISA). A questionnaire was used to collect data on the potential risk factors. The study revealed flock and animal level seroprevalence of 58.3% (109/187; 95% confidence interval [CI]:,51.16, 65.42)

and 19.7% (183/927; 95% CI: 17.17, 22.31), respectively. The likelihood of acquiring T. gondii infection was higher in semi-intensively managed goats (Odds ratio [OR] = 2.48, 95% confidence interval [CI]: 1.14, 5.37; P = 0.022) than in extensively managed goats, in females than in males (OR = 1.84, 95% CI: 1.16, 2.92; P = 0.010), in adults than in young animals (OR = 2.00, 95% CI: 1.21, 3.28; P = 0.006), in small than in large flocks (OR = 2.03, 95% CI: 1.03, 3.98; P = 0.040), in goats kept under sedentary (OR = 2.81, 95% CI: 1.41, 5.59; P = 0.003) and agropastoral farming system (OR = 3.62, 95% Apoptosis inhibitor CI: 1.83, 7.18; P < 0.001) than pastoral farming system and in goats allowed to drink water from the tap than those drinking from river and stagnant water bodies (OR = 9.25, 95% CI: 3.04, 28.15; P < 0.001). Our study indicates that exposure of goats to oocysts of T. gondii is widespread. We recommend further studies to determine the genotype of the parasite, public health and economic impacts of toxoplasmosis and the role of raw goat meat and milk as a source of infection for consumers. (C) 2012 Elsevier Ltd. All rights reserved.

However, with regard to existing meta-analyses, a wide variety of different methods have been employed, often with no evident rationale for using a particular PU-H71 research buy approach. More specifically, the approach to dealing with zero events varies, and guidelines on this issue would be desirable.”
“The reaction of 4-hydroxycoumarin

with 2-acetyloxiranes in dimethylformamide in the presence of triethylamine gave 2,3-dihydro-4H-furo[3,2-c]chromen-4-ones which were converted into 4H-furo[3,2-c]-chromen-4-one derivatives as a result of dehydration or fragmentation.”
“Background:The Disease State Index (DSI) is a method which interprets data originating from multiple different sources, assisting the clinician in the diagnosis and follow-up of dementia diseases. Objective: We compared the differences in accuracy in differentiating stable mild cognitive impairment (S-MCI) and progressive MCI (P-MCI) obtained from different data combinations using the DSI. Methods: We investigated 212 cases with S-MCI and 165 cases with P-MCI from the Alzheimer’s Disease Neuroimaging Initiative cohort. Data from neuropsychological tests, cerebrospinal fluid, apolipoprotein E (APOE) genotype, magnetic resonance imaging

(MRI) and positron emission tomography (PET) were included. Results: The combination of all parameters gave the highest accuracy (accuracy 0.70, sensitivity 0.71, specificity 0.68). In the different Compound C categories, neuropsychological tests (0.65, 0.65, 0.65) and hippocampal volumetry (0.66, 0.66, 0.66) achieved the highest accuracy. Conclusion: In addition to neuropsychological testing, MRI is recommended to be included for differentiating S-MCI from P-MCI. APOE genotype, CSF and PET may provide some additional information. (C) 2013 S. Karger AG, Basel”
“A meta-analysis of isoniazid preventive therapy (IPT) in

human immunodeficiency virus-positive individuals failed to show a mortality benefit even though tuberculosis is a leading cause of death in this group. Results for purified protein derivative (PPD) positive patients were ABT-737 ic50 heterogeneous, however, and two of the included trials had many PPD-unknowns. When all PPD-unknowns were allocated to either PPD-positive or PPD-negative, the individual trial results were not robust, and simulated meta-analyses showed an overall reduction in all-cause mortality for PPD-positive individuals on IPT (relative risk 0.76; 95% credibility interval 0.6-0.95).”
“Background: To assess potential long-term consequences of cancer treatment, studies that include comparison groups are needed. These comparison groups should be selected in a way that allows the subtle long-range effects of cancer therapy to be detected and distinguishes them from the effects of aging and other risk factors.